The goal of this project is to investigate how a major cholesterol carrying protein of humans, apolipoprotein E (apo E), responds to changes in dietary cholesterol. It is our hypothesis that the capacity of humans to metabolize dietary cholesterol is determined by genetic factors which influence apo E metabolism and that these factors vary greatly from one individual to another. Two projects are proposed which will center around our recent discoveries of differences between individuals in apo E metabolism: 1) A study of apo E patterns in patients with severe coronary artery disease in comparison to normal individuals without disease. This will determine if a particular apo I phenotype predisposes to coronary artery disease; and 2) Measurements in both monkeys and humans of plasma total apo E levels and apo E levels of lipoprotein particles in the density range 1.01-1.12 gm/ml when they are fed a cholesterol-free diet and after dietary challenge with cholesterol. Our prelimary data indicate that apo E levels in this density region provide an index of an animal's ability to handle a given dietary cholesterol intake. Using the results of this work, we will be able to identify a high risk group in the population which is at increased risk for early coronary disease due to consumption of cholesterol present in the average diet.